All human breast cancer contains either or both steroid alcohol and estrogen sulfotransferases. By contrast, normal breast tissue is either devoid of or contains very low levels of these same enzymes. Accordingly, compounds are to be synthesized that resemble both substrates and as well the transition state of the reactions mediated by estrogen and steroid (alcohol) sulfotransferases as novel, specific and potentially potent (mammary) antitumor agents. Representative examples of such transition-state (multisubstrate) analogs to be synthesized include 3P1-estrone-5'P2-(3'-phosphoribo-nucleoside) pyrophosphates. The latter are, in turn, to be comprised of those estrogens and ribonucleoside 3', 5'-diphosphates that have proved most effective (individually) in the inhibition of enzymic sulfurylation by 3'-phosphoadenosine 5'-phosphosulfate (PAPS). Similarly, 3'P1-estrogen 5'-P2-ribonucleoside methylenediphosphonates are to be prepared for corresponding biochemical evaluation. In addition, methylene-bridged adenosine-estrogen derivatives are to be prepared to amplify the scope of synthetic endeavor in the search for specific and potent novel antitumor agents. It is proposed to isolate steroid alcohol sulfotransferase from human breast tumor cell line (MCF-7) and to characterize substrate requirements and inhibitors of the enzyme. Compounds that prove successful in blocking estrogen and steroid alcohol sulfotransferase will be examined for effects in rat (DMBA-induced) tumor slices and MCF-7 cell culture preliminary to in vivo screening.